Process for the manufacture of 6-alkoxy-8-aminoquinolines



Patented Sept. 17, 1929 UNITED sTATEs PATENT OFFICE WERNER S CHULEMANN, OF VOH'WINKEL, NEAR ELBERFEIJ), AND FRITZ SCHON- HOFER AND AUGUST WINGLER, OF ELBERFELD, GERMANY, ASSIGNORS TO WIN- THIROP CHEMICAL COMPANY, INC., OI NEW YORK, N. Y., A CORPORATION OF NEW YORK PROCESS FOR THE MANUFACTURE or 6-ALKOXY-8-AMINOQUINOLINES No Drawing. Application filed January 21, 1928, Serial No. 248,562, and in Germany January 28, 1927.

The present invention is a modification of the process protected in the specificatlon Ser. No. 85,030 filed January 30, 1926 for the manufacture of 6-allroxy-8-aminoquinolines, and consists in subjecting 6-alkoxy-- 10 the hydrazides, treating the latter with nitrous acid to form the azides, treating the azides with an alcohol to obtain the urethanes and treating the ure'thanes with a saponifying agent, e. g. with acids or alkalies, to obtain the amines. The reaction proceeds according to the following scheme:

hydrazine, which separates out, is filtered ofl' its melting point is 178 to 179 C.

4.3 grams of this hydrazide are dissolved in 50 cc. of normal hydrochloric acid and 14 cc. of 10% sodium nitrite solution are slowly added, the whole being cooled in ice.- The azide precipitates and after being rendered alkaline is extracted with ether. The ethereal solution is dried with calcium chloride and an equal volume of absolute alcohol is added thereto, when the mixed solution is evaporated on the water-bath to a quarter of the total volume. When the evolution of'nitrogen has ceasedthe evaporation is completed to dryness. The urethane derivative has a melting point of 76 to R GOOR +R CONH NIT- R CO 'N R -NH- COO R R NH R stands for a quinoline radicle, R for an alkyl, aryl or aralkyl radicle.

In accordance with the specification Serial No. 85,030, 6-alkoxy-S-aminbquinolines are produced by reducing by the customary methods-8-nitro or 8-azo-derivatives of 6- 5 alkoxyquinolines or by alkylating 6-hydroxy-S-aminoquinoline or its N-substitution products on the hydroxyl' oxygen and if desired converting the derivatives of 6- alkoXy-S-aminoquinolines thus obtainable, which are substituted in the nitrogen atom into the free amino compound.

In accordance with the present invention the same compoundscan' also be produced in a technically excellent manner from 6-alkoxyquinoline-B-carboxylic acid alkyl esters according to the Curtius reaction, as already indicated.

The following example will illustrate our invention: r Ewample.10 grams of 6-methoxyquin0- line-8-carboxylic acid ethyl ester, melting at 62 to 63 C., are heated under' refiux for 3 hours with 10 grams of alcohol and 5 grams of hydrazine hydrate. After cooling. the

hydrazides with nitrous acid to obtain theazides, treating the azides with an alcohol to obtain. the urethanes urethanes with a tain the amines.

2. In the process for the manufacture of 6-methoxy-8-aminoquinoline, the step which comprises subjecting 6-metho quinoline-8- carboxylic acid esters to the %urtius reac tion by treating them with hydrazine h drate to form the hydrazides, treating t e hydrazides with nitrous acid to obtain the azides, treating the azides with an alcohol and treating the Isaponifying agent to obto obta the uretha e an treating the urethanes with a saponifying agent to obtain the amine.

, 3. In the process for the manufacture of 6-methoxy-8-aminoquino1ine the step which 5' comprises subjecting 6-methoxyquino1ine-8- carboxylic acid ethylie ester to the Curtius reaction b treating it with hydrazine hydrate, to orm the hydrazide, treating the hydrazide with nitrous acid to obtain the 10 azide, treating the azide with ethyl alcohol to obtain the urethane and treating the urethane with slaked lime to obtain the amine;

In testimony whereof we have hereunto set 5 our hands.

WERNER SCHULEMANN.

FRITZ SCHONHCFER. AUGUST WINGLER. 

